title: Four microRNAs promote prostate cell proliferation with regulation of PTEN and its downstream signals in vitro.
abstract: BACKGROUND
  Phosphatase and tensin homologue (PTEN), as a tumor suppressor, plays vital roles in tumorigenesis and progression of prostate cancer. However, the mechanisms of PTEN regulation still need further investigation. We here report that a combination of four microRNAs (miR-19b, miR-23b, miR-26a and miR-92a) promotes prostate cell proliferation by regulating PTEN and its downstream signals in vitro.
  
  
  RESULTS
  We found that the four microRNAs (miRNAs) could effectively suppress PTEN expression by directly interacting with its 3' UTR in prostate epithelial and cancer cells. Under-expression of the four miRNAs by antisense neutralization up-regulates PTEN expression, while overexpression of the four miRNAs accelerates epithelial and prostate cancer cell proliferation. Furthermore, the expression of the four miRNAs could, singly or jointly, alter the expression of the key components in the phosphoinositide 3-kinase (PI3K)/Akt pathway, including PIK3CA, PIK3CD, PIK3R1 and Akt, along with their downstream signal, cyclin D1.
  
  
  CONCLUSIONS
  These results suggested that the four miRNAs could promote prostate cancer cell proliferation by co-regulating the expression of PTEN, PI3K/Akt pathway and cyclin D1 in vitro. These findings increase understanding of the molecular mechanisms of prostate carcinogenesis and progression, even provide valuable insights into the diagnosis, prognosis, and rational design of novel therapeutics for prostate cancer.
authors.affiliation: State Key Laboratory of Genetic Engineering and Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China ; Experimental Research Center and Cancer Center, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.forename: Yu-xiang
authors.initials: YX
authors.lastname: Fang
authors.forename: Jing-lun
authors.initials: JL
authors.lastname: Xue
authors.forename: Jin-zhong
authors.initials: JZ
authors.lastname: Chen
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008156:Luciferases; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011467:Prostate / Q000166:cytology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; D008156:Luciferases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human